2. Academic Validation
  3. Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes

Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes

  • Bioorg Med Chem. 2015 Aug 1;23(15):4230-4236. doi: 10.1016/j.bmc.2015.06.043.
Hsueh-Yun Lee 1,  Chih-Yi Chang 1,  Mei-Jung Lai 2,  Hsun-Yueh Chuang 1,  Ching-Chuan Kuo 3,  Chi-Yen Chang 4,  Jang-Yang Chang 5,  Jing-Ping Liou 6
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
  • 2 Center for Translational Medicine, Taipei Medical University, Taiwan.
  • 3 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan.
  • 4 National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan.
  • 5 National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: jychang@nhri.org.tw.
  • 6 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan; School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Section 6, Taipei 114, Taiwan. Electronic address: jpl@tmu.edu.tw.
PMID: 26160020 DOI: 10.1016/j.bmc.2015.06.043
Abstract

This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy-3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC50 values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A-ring of this compound not only retains the biological activity but has valuable physicochemical properties.

Keywords

Antiproliferative; CA-4; Vascular-disrupting agents.

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